title: Coordinated and unique functions of the E-selectin ligand ESL-1 during inflammatory and hematopoietic recruitment in mice.
abstract: Beyond its well-established roles in mediating leukocyte rolling, E-selectin is emerging as a multifunctional receptor capable of inducing integrin activation in neutrophils, and of regulating various biological processes in hematopoietic precursors. Although these effects suggest important homeostatic contributions of this selectin in the immune and hematologic systems, the ligands responsible for transducing these effects in different leukocyte lineages are not well defined. We have characterized mice deficient in E-selectin ligand-1 (ESL-1), or in both P-selectin glycoprotein-1 (PSGL-1) and ESL-1, to explore and compare the contributions of these glycoproteins in immune and hematopoietic cell trafficking. In the steady state, ESL-1 deficiency resulted in a moderate myeloid expansion that became more prominent when both glycoproteins were eliminated. During inflammation, PSGL-1 dominated E-selectin binding, rolling, integrin activation, and extravasation of mature neutrophils, but only the combined deficiency in PSGL-1 and ESL-1 completely abrogated leukocyte recruitment. Surprisingly, we find that the levels of ESL-1 were strongly elevated in hematopoietic progenitor cells. These elevations correlated with a prominent function of ESL-1 for E-selectin binding and for migration of hematopoietic progenitor cells into the bone marrow. Our results uncover dominant roles for ESL-1 in the immature compartment, and a functional shift toward PSGL-1 dependence in mature neutrophils.
authors.affiliation: Department of Epidemiology, Atherothrombosis and Imaging, Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro 3, Madrid, Spain;
authors.forename: Vinatha
authors.initials: V
authors.lastname: Sreeramkumar
authors.forename: Magdalena
authors.initials: M
authors.lastname: Leiva
authors.forename: Anika
authors.initials: A
authors.lastname: Stadtmann
authors.forename: Christophe
authors.initials: C
authors.lastname: Pitaval
authors.forename: Inés
authors.initials: I
authors.lastname: Ortega-Rodríguez
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
authors.forename: Alexander
authors.initials: A
authors.lastname: Zarbock
authors.forename: Andrés
authors.initials: A
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D036904:Leukocyte Rolling / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
chemical_list: D019040:E-Selectin; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor